Chemical carcinogens Flashcards

(34 cards)

1
Q

what is 3,4-benzypyrene oxidised by and to

A

glutathione s-transferases to 7,8-epoxide metabolite

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2
Q

where is p53 highly active

A

malignant cells

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3
Q

what does error-prone DNA replication require

A

DNA polymerases delta and epsilon

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4
Q

Which cytochromes biotransforms polycyclic aromatic hydrocarbons (4)

A
  1. P450
  2. 1A1
  3. 1A2
  4. 1B1
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5
Q

what is the formation of epoxides catalysed by

A

UDP-dependent glycuronosyl transferases

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6
Q

what is the chemically structure of polycyclic aromatic hydrocarbons

A

carbon and hydrogen arranged into aromatic rings

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7
Q

what do all major carcinogens in this group contain

A

bay region

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8
Q

what does the K region contain

A

higher electron density

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9
Q

what is a imbalance between K and L regions suggested to cause

A

carcinogenicity

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10
Q

what can epoxides form

A

K regions

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11
Q

what occurs during nucleotide excision repair

A

repairing of DNA damage with low fidelity

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12
Q

where are polycyclic aromatic hydrocarbons in the environment from

A

anthropogenic sources

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13
Q

where is the aryl hydrocarbon receptor found

A

nucleus of hepatocytes

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14
Q

what excretes polycyclic aromatic hydrocarbons

A

kidneys

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15
Q

what do the bay regions bind with in particular

A

NH2 group of guanine

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16
Q

what kind of molecules are PAHs

A

planar molecules

17
Q

what do most PAHs contain

A

phenanthrene nucleus

18
Q

where in the plenanthrene moiety is the bay region located

19
Q

what increases carcinogenicity

A

addition of other planar ring systems to C6C7

20
Q

two types of cancer

A

benign and malignant

21
Q

three most common classifications of cancer and where do they develop

A
  1. carcinomas - epithelial cells
  2. sarcomas - bone and muscle
  3. leukaemia - blood
22
Q

five classes of chemical carcinogens

A
  1. alkylating agents
  2. nitroso compounds
  3. azo dyes
  4. aromatic amines
  5. polycyclic aromatic hydrocarbons (PAHs)
23
Q

when are PAHs generated

A

whenever organic materials are burned

24
Q

when was the association between cancer and PAHs first noted

25
what do the diol-epoxides of 3,4-benzypyrene normally bind to?
guanine residues of DNA
26
what correlations were found between carcinogenic activity and electron density
high electron density resulted in greater carcinogenic activity
27
what do PAHs form and what is this reaction catalysed by?
K-region epoxides catalysed by cytochrome p450
28
why are epoxides dangerous?
they react directly with DNA forming mutagens and carcinogenic activity
29
what became clear by the 1970s regarding epoxides
that non-K-region exoxides could exist
30
how do the diol-epixodes of 3,4-benzpryene bind to guanine
covalent bond is formed between C10 of benzo(a)pyrene and the exocyclic 2-amino
31
why does binding of PAH cause damage to DNA
repair is not always accurate leading to point mutations
32
what do 10% of human tumours contain
mutations of ras genes
33
what is different about oncogenic p21
it has lost its GTPase activity = constant signalling for growth
34
how to measure PAH exposure
electrophilic metabolites of PAHs form covalent adducts with albumin and haemoglobin which can then be assayed